Monoclonal antibodies have been shown to represent, as a class of molecules, important therapeutic proteins with application in various disease states. The goal of GenPharm's program is to provide access to the human immunoglobulin repertoire such that human monoclonal antibodies can be isolated in an analogous manner to rodent monoclonal antibodies. The goal of Phase II is to generate transgenic mice that make high affinity IgG antibodies containing human heavy chains. The transgene expressing B cells will undergo affinity maturation in response to a wide variety of antigens. Transgenic mice that express human immunoglobulin light chains will also be generated. The two strains of transgenic mice will be bred together to generate a mouse that can be used to make mouse hybridomas secreting fully human monoclonal antibodies.